The impact of low energy proton damage on the operational characteristics of EPIC-MOS CCDs

The University of Tübingen 3.5 MeV Van de Graaf accelerator facility was used to investigate the effect of low energy protons on the performance of the European Photon Imaging Camera (EPIC), metal–oxide semiconductor (MOS), charge coupled devices (CCDs). Two CCDs were irradiated in different parts of their detecting areas using different proton spectra and dose rates. Iron-55 was the calibration source in all cases and was used to measure any increases in charge transfer inefficiency (CTI) and spectral resolution of the CCDs. Additional changes in the CCD bright pixel table and changes in the low X-ray energy response of the device were examined. The Monte Carlo code Stopping Range of Ions in Matter (SRIM) was used to model the effect of a 10 MeV equivalent fluence of protons interacting with the CCD. Since the non-ionising energy loss (NIEL) function could not be applied effectively at such low proton energies. From the 10 MeV values, the expected CTI degradation could be calculated and then compared to the measured CTI changes

Evidence of potential establishment of pink salmon Oncorhynchus gorbuscha in Scotland.

In spring 2022, pink salmon Oncorhynchus gorbuscha smolts were recorded in the UK. Fish were caught in the Rivers Thurso and Oykel in Scotland between 13 and 17 March. To the authors' knowledge, this is the first observation of O. gorbuscha smolts in Europe outside the Scandinavian and Kola peninsulas, including other tributaries of the White and Barents Seas. It also provides evidence of successful spawning in 2021 and completion of the freshwater phase of the life cycle, and indicates the possibility for potential establishment of an O. gorbuscha population in Great Britain

Apremilast monotherapy in DMARD-naive psoriatic arthritis patients: Results of the randomized, placebocontrolled PALACE 4 trial

Objectives. The PALACE 4 trial evaluated apremilast monotherapy in patients with active PsA who were DMARD-naive. Methods. Eligible patients were randomized (1:1:1) to placebo, apremilast 20mg twice a day or apremilast 30mg twice a day. At week 16 or 24, placebo patients were rerandomized to apremilast. Double-blind apremilast treatment continued to week 52, with extension up to 4 years. The primary endpoint was the proportion of patients achieving ≥20% improvement in ACR response criteria (ACR20) at week 16; secondary endpoints included the mean change in the HAQ Disability Index (HAQ-DI) score at week 16. Results. A total of 527 patients with mean disease duration of 3.4 years and high disease activity were randomized and received treatment. More apremilast patients achieved ACR20 response at week 16 [placebo, 15.9%; 20 mg, 28.0% (P = 0.0062); 30 mg, 30.7% (P = 0.0010)]. The mean HAQ-DI improvements were -0.17 (20 mg; P = 0.0008) and -0.21 (30 mg; P<0.0001) vs 0.03 (placebo). Both apremilast doses showed significant ACR50 responses vs placebo at week 16 and improvements in secondary efficacy measures (swollen/tender joint counts) and psoriasis assessments, with sustained improvements through week 52. Common adverse events (AEs) over 52 weeks were diarrhoea, nausea, headache and upper respiratory tract infection; most events were mild or moderate. Serious AEs and AEs leading to discontinuation were comparable between groups. Laboratory abnormalities were infrequent and transient. Conclusions. In DMARD-naive patients, apremilast monotherapy improved PsA signs/symptoms over 52 weeks and was generally well tolerated

Ionic high-pressure form of elemental boron

Boron is an element of fascinating chemical complexity. Controversies have shrouded this element since its discovery was announced in 1808: the new 'element' turned out to be a compound containing less than 60-70 percent of boron, and it was not until 1909 that 99-percent pure boron was obtained. And although we now know of at least 16 polymorphs, the stable phase of boron is not yet experimentally established even at ambient conditions. Boron's complexities arise from frustration: situated between metals and insulators in the periodic table, boron has only three valence electrons, which would favour metallicity, but they are sufficiently localized that insulating states emerge. However, this subtle balance between metallic and insulating states is easily shifted by pressure, temperature and impurities. Here we report the results of high-pressure experiments and ab initio evolutionary crystal structure predictions that explore the structural stability of boron under pressure and, strikingly, reveal a partially ionic high-pressure boron phase. This new phase is stable between 19 and 89 GPa, can be quenched to ambient conditions, and has a hitherto unknown structure (space group Pnnm, 28 atoms in the unit cell) consisting of icosahedral B12 clusters and B2 pairs in a NaCl-type arrangement. We find that the ionicity of the phase affects its electronic bandgap, infrared adsorption and dielectric constants, and that it arises from the different electronic properties of the B2 pairs and B12 clusters and the resultant charge transfer between them.Comment: Published in Nature 453, 863-867 (2009

A biophysical model of cell adhesion mediated by immunoadhesin drugs and antibodies

A promising direction in drug development is to exploit the ability of natural killer cells to kill antibody-labeled target cells. Monoclonal antibodies and drugs designed to elicit this effect typically bind cell-surface epitopes that are overexpressed on target cells but also present on other cells. Thus it is important to understand adhesion of cells by antibodies and similar molecules. We present an equilibrium model of such adhesion, incorporating heterogeneity in target cell epitope density and epitope immobility. We compare with experiments on the adhesion of Jurkat T cells to bilayers containing the relevant natural killer cell receptor, with adhesion mediated by the drug alefacept. We show that a model in which all target cell epitopes are mobile and available is inconsistent with the data, suggesting that more complex mechanisms are at work. We hypothesize that the immobile epitope fraction may change with cell adhesion, and we find that such a model is more consistent with the data. We also quantitatively describe the parameter space in which binding occurs. Our results point toward mechanisms relating epitope immobility to cell adhesion and offer insight into the activity of an important class of drugs.Comment: 13 pages, 5 figure

Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis

Background Ultrasound (US) has largely replaced contrast venography as the definitive diagnostic test for deep vein thrombosis (DVT). We aimed to derive a definitive estimate of the diagnostic accuracy of US for clinically suspected DVT and identify study-level factors that might predict accuracy. Methods We undertook a systematic review, meta-analysis and meta-regression of diagnostic cohort studies that compared US to contrast venography in patients with suspected DVT. We searched Medline, EMBASE, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, Database of Reviews of Effectiveness, the ACP Journal Club, and citation lists (1966 to April 2004). Random effects meta-analysis was used to derive pooled estimates of sensitivity and specificity. Random effects meta-regression was used to identify study-level covariates that predicted diagnostic performance. Results We identified 100 cohorts comparing US to venography in patients with suspected DVT. Overall sensitivity for proximal DVT (95% confidence interval) was 94.2% (93.2 to 95.0), for distal DVT was 63.5% (59.8 to 67.0), and specificity was 93.8% (93.1 to 94.4). Duplex US had pooled sensitivity of 96.5% (95.1 to 97.6) for proximal DVT, 71.2% (64.6 to 77.2) for distal DVT and specificity of 94.0% (92.8 to 95.1). Triplex US had pooled sensitivity of 96.4% (94.4 to 97.1%) for proximal DVT, 75.2% (67.7 to 81.6) for distal DVT and specificity of 94.3% (92.5 to 95.8). Compression US alone had pooled sensitivity of 93.8 % (92.0 to 95.3%) for proximal DVT, 56.8% (49.0 to 66.4) for distal DVT and specificity of 97.8% (97.0 to 98.4). Sensitivity was higher in more recently published studies and in cohorts with higher prevalence of DVT and more proximal DVT, and was lower in cohorts that reported interpretation by a radiologist. Specificity was higher in cohorts that excluded patients with previous DVT. No studies were identified that compared repeat US to venography in all patients. Repeat US appears to have a positive yield of 1.3%, with 89% of these being confirmed by venography. Conclusion Combined colour-doppler US techniques have optimal sensitivity, while compression US has optimal specificity for DVT. However, all estimates are subject to substantial unexplained heterogeneity. The role of repeat scanning is very uncertain and based upon limited data

Measuring errors and violations on the road: A bifactor modeling approach to the Driver Behavior Questionnaire

The Driver Behavior Questionnaire (DBQ) is a self-report measure of driving behavior that has been widely used over more than 20 years. Despite this wealth of evidence a number of questions remain, including understanding the correlation between its violations and errors sub-components, identifying how these components are related to crash involvement, and testing whether a DBQ based on a reduced number of items can be effective. We address these issues using a bifactor modeling approach to data drawn from the UK Cohort II longitudinal study of novice drivers. This dataset provides observations on 12,012 drivers with DBQ data collected at .5, 1, 2 and 3 years after passing their test. A bifactor model, including a general factor onto which all items loaded, and specific factors for ordinary violations, aggressive violations, slips and errors fitted the data better than correlated factors and second-order factor structures. A model based on only 12 items replicated this structure and produced factor scores that were highly correlated with the full model. The ordinary violations and general factor were significant independent predictors of crash involvement at 6 months after starting independent driving. The discussion considers the role of the general and specific factors in crash involvemen

Why did Donders, after describing pseudotorsion, deny the existence of ocular counterrolling together with Ruete, Volkmann, von Graefe and von Helmholtz, until Javal reconfirmed its existence?

After the rapid spread of strabismus surgery by total tenotomy, which had been proposed by the orthopedist Louis Stromeyer from Göttingen in 1838 and performed by the plastic surgeon Johann Friedrich Dieffenbach on October 26th and by the ophthalmologist Florent Cunier on October 29th, 1839, brilliant researchers studied the physiology of eye movements, resulting in the laws by Franciscus Cornelis Donders on pseudotorsion in tertiary positions of gaze and by Johann Benedict Listing that each eye position can be reached by rotation about an axis perpendicular to the primary and the new position of gaze. John Hunter had first described ocular counterrolling (OCR) with head tilt in 1786. The anatomist Alexander Friedrich von Hueck inferred from anatomical studies, however, that up to 28.6° OCR would be possible onhead-tilt to right or left shoulder in 1838, and estimated his own OCR seen in a mirror at approximately 25°. Donders, Christian Georg Theodor Ruete, Alfred Wilhelm Volkmann, Albrecht von Graefe and Hermann von Helmholtz subsequently denied the existence of OCR for many years and thought that only pseudotorsion existed. Louis Emile Javal had myopia and astigmatism, and he re-established the existence of OCR in 1867 when he noticed that, on head tilt to either shoulder, the axis of astigmatism of his eyes no longer coincided with the axis of astigmatism of his glasses

Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

Peer reviewedPublisher PD